LRRC23

Chr 12AR

leucine rich repeat containing 23

Also known as: LRPB7, SPGF92

NCBI Gene: 10233 ENSG00000010626 OMIM: 620708

The protein is essential for sperm motility and male fertility, specifically required for proper assembly of radial spoke structures in sperm flagella. Mutations cause spermatogenic failure 92, inherited in an autosomal recessive pattern. This gene shows low constraint against loss-of-function variants (LOEUF 1.218), consistent with its specialized role in male reproductive function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Involved in flagellated sperm motility and radial spoke assembly. Located in cytoplasm and sperm flagellum. Implicated in spermatogenic failure 92. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.221 OMIM phenotype

Clinical Summary— LRRC23

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 47 VUS of 61 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.87

OE 0.78 (0.51–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.25Z-score

OE missense 0.95 (0.84–1.07)

176 obs / 185.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.51–1.22)

0≤0.351.4

Missense OE?0.95 (0.84–1.07)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 14 / 18.0Missense obs/exp: 176 / 185.7Syn Z: 0.41

This gene — mechanism propensity

0.6551th %ile

GOF

0.6053th %ile

LOF

0.3260th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS47

Likely Benign2

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	2	0	2
Likely Pathogenic	0	0	0
VUS	0	47	47
Likely Benign	0	2	2
Benign	0	0	0
Total	2	49	51

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

47 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap LRRC23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →